Studies concerning the manner in which exposure to elevated glucose concentrations and the associated increase in polyol pathway activity induce alterations in the metabolism of the aortic wall will be continued; these studies will center on the factors responsible for the decrease in aortic free myoinositol content, and an examination of the associated changes in inositol containingg phospholipids. Studies to develop an aortic preparation in which intact endothelium is preserved during incubation will be continued. This preparation will be employed to examine the glucose utilization of the preparation, its response to insulin and other hormones, and the changes induced by exposure to high glucose concentrations. Studies of the relationship of alterations in myoinositol metabolism to the development of experimental diabetic neuropathy will be continued. The changes in human renal glomerular basement membrane composition that occur with ageing and with diabetes of varying duration will be determined in kidneys obtained at autopsy.